Inhibitory effects on mitochondrial complex I of semisynthetic mono-Tetrahydrofuran acetogenin derivatives

Modifications in the terminal α,β-unsaturated γ-methyl-γ-lactone moiety or in the alkyl chain that links this terminal γ-lactone with the α,α′-dihydroxylated THF system of the natural mono-tetrahydrofuranic acetogenins, annonacin and annonacinone, led to the preparation of eight semisynthetic derivatives. Their inhibitory effects on mitochondrial complex I is discussed and compared with that of the classical complex I inhibitor, rotenone.